The proposed investigation will comprise four major areas of study. Studies will be carried out the detection and isolation of tissue-specific, group-specific, and tumor-specific antigens, as well as the basic conditions leading to autoantibody formation, and the possible tissue injury following active and passive autoimmunization. The controlling mechanisms of immunological responsiveness and self recognition which seem to be under genetic influence will be studied. Mechanisms of antibody-mediated and cell-mediated tissue damage will be explored both in vivo and in vitro using a variety of techniques and approaches ranging from physiochemical studies of the surface of activated lymphoid and mononuclear cells to in vivo studies of specific and non-specific factors influencing the migration of immunocompetent lymphocytes. In connection with the search for tumor-related antigens this information will be considered in the light of the possibility of an immunological approach to the detection and treatment of animal and human malignancies.